Geetika Aggarwal, Subhashis Banerjee, Spencer A Jones, Yousri Benchaar, Jasmine Bélanger, Myriam Sévigny, Denise M Smith, Michael L Niehoff, Monica Pavlack, Ian Mitchelle S de Vera, Terri L Petkau, Blair R Leavitt, Karen Ling, Paymaan Jafar-Nejad, Frank Rigo, John E Morley, Susan A Farr, Paul A Dutchak, Chantelle F Sephton, Andrew D Nguyen
Heterozygous GRN (progranulin) mutations cause frontotemporal dementia (FTD) due to haploinsufficiency, and increasing progranulin levels is a major therapeutic goal. Several microRNAs, including miR-29b, negatively regulate progranulin protein levels. Antisense oligonucleotides (ASOs) are emerging as a promising therapeutic modality for neurological diseases, but strategies for increasing target protein levels are limited. Here, we tested the efficacy of ASOs as enhancers of progranulin expression by sterically blocking the miR-29b binding site in the 3' UTR of the human GRN mRNA...
November 17, 2023: Journal of Biological Chemistry